Chromosomes and Human Genetics

1. Chromosomes andHuman Genetics Chapter 12

2. Chromosomes & Cancer • Some genes on chromosomes control cell growth and division • If something affects chromosome structure at or near these loci, cell division may spiral out of control • This can lead to cancer

3. Philadelphia Chromosome • First abnormal chromosome to be associated with a cancer • Reciprocal translocation • Causes chronic myelogenous leukemia (CML)

4. Genes • Units of information about heritable traits • In eukaryotes, distributed among chromosomes • Each has a particular locus • Location on a chromosome

5. Homologous Chromosomes • Homologous autosomes are identical in length, size, shape, and gene sequence • Sex chromosomes are nonidentical but still homologous • Homologous chromosomes interact, then segregate from one another during meiosis

6. Alleles • Different molecular forms of a gene • Arise through mutation • Diploid cell has a pair of alleles at each locus • Alleles on homologous chromosomes may be same or different

7. Sex Chromosomes • Discovered in late 1800s • Mammals, fruit flies • XX is female, XY is male • In other groups XX is male, XY female • Human X and Y chromosomes function as homologues during meiosis

8. Karyotype Preparation - Stopping the Cycle • Cultured cells are arrested at metaphase by adding colchicine • This is when cells are most condensed and easiest to identify

9. Karyotype Preparation • Arrested cells are broken open • Metaphase chromosomes are fixed and stained • Chromosomes are photographed through microscope • Photograph of chromosomes is cut up and arranged to form karyotype diagram

10. Karyotype Diagram 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 XX (or XY) Figure 12.4Page 197

11. X X x X Y x Y X X X XX XX XY XY Sex Determination female (XX) male (XY) eggs sperm Figure 12.5Page 198

12. The Y Chromosome • Fewer than two dozen genes identified • One is the master gene for male sex determination • SRY gene (sex-determining region of Y) • SRY present, testes form • SRY absent, ovaries form

13. The X Chromosome • Carries more than 2,300 genes • Most genes deal with nonsexual traits • Genes on X chromosome can be expressed in both males and females

14. Discovering Sex Linkage homozygous dominant female recessive male x Gametes: X X X Y All F1 have red eyes x Gametes: X X X Y 1/2 1/2 1/4 1/2 1/2 1/4 1/4 F2 generation: 1/4 Figure 12.7Page 200

15. Crossover Frequency Proportional to the distance that separates genes A B C D Crossing over will disrupt linkage between A and B more often than C and D In-text figurePage 201

16. Linkage Mapping in Humans • Linkage maps based on pedigree analysis through generations • Color blindness and hemophilia are very closely linked on X chromosome

17. Pedigree Symbols male female marriage/mating offspring in order of birth, from left to right Individual showing trait being studied sex not specified generation I, II, III, IV... Figure 12.9aPage 202

18. I II III IV V *Gene not expressed in this carrier. Pedigree for Polydactyly female male 5,5 6,6 * 5,5 6,6 6,6 5,5 6,6 5,5 6 7 5,5 6,6 5,5 6,6 5,5 6,6 5,5 6,6 5,6 6,7 12 6,6 6,6 Figure 12.9bPage 202

19. Genetic Abnormality • A rare, uncommon version of a trait • Polydactyly • Unusual number of toes or fingers • Does not cause any health problems • View of trait as disfiguring is subjective

20. Genetic Disorder • Inherited conditions that cause mild to severe medical problems • Why don’t they disappear? • Mutation introduces new rare alleles • In heterozygotes, harmful allele is masked, so it can still be passed on to offspring

21. Autosomal Recessive Inheritance Patterns • If parents are both heterozygous, child will have a 25% chance of being affected Figure 12.10aPage 204

22. enzyme 3 enzyme 1 enzyme 2 galactose-1- phosphate galactose-1- phosphate lactose galactose +glucose intermediate in glycolysis Galactosemia • Caused by autosomal recessive allele • Gene specifies a mutant enzyme in the pathway that breaks down lactose In-text figurePage 204

23. Autosomal Dominant Inheritance Trait typically appears in every generation Figure 12.10bPage 204

24. Huntington Disorder • Autosomal dominant allele • Causes involuntary movements, nervous system deterioration, death • Symptoms don’t usually show up until person is past age 30 • People often pass allele on before they know they have it

25. Achondroplasia • Autosomal dominant allele • In homozygous form usually leads to stillbirth • Heterozygotes display a type of dwarfism • Have short arms and legs relative to other body parts

26. X-Linked Recessive Inheritance • Males show disorder more than females • Son cannot inherit disorder from his father Figure 12.12aPage 205

27. Examples of X-Linked Traits • Color blindness • Inability to distinguish among some of all colors • Hemophilia • Blood-clotting disorder • 1/7,000 males has allele for hemophilia A • Was common in European royal families

28. Fragile X Syndrome • An X-linked recessive disorder • Causes mental retardation • Mutant allele for gene that specifies a protein required for brain development • Allele has repeated segments of DNA

29. Hutchinson-Gilford Progeria • Mutation causes accelerated aging • No evidence of it running in families • Appears to be dominant • Seems to arise as spontaneous mutation • Usually causes death in early teens

30. Duplication • Gene sequence that is repeated several to hundreds of times • Duplications occur in normal chromosomes • May have adaptive advantage • Useful mutations may occur in copy

31. Duplication normal chromosome one segment repeated three repeats

32. Inversion A linear stretch of DNA is reversed within the chromosome segments G, H, I become inverted In-text figurePage 206

33. Translocation • A piece of one chromosome becomes attached to another nonhomologous chromosome • Most are reciprocal • Philadelphia chromosome arose from a reciprocal translocation between chromosomes 9 and 22

34. Translocation In-text figurePage 206 one chromosome a nonhomologous chromosome nonreciprocal translocation In-text figurePage 206

35. Deletion • Loss of some segment of a chromosome • Most are lethal or cause serious disorder

36. Aneuploidy • Individuals have one extra or less chromosome • (2n + 1 or 2n - 1) • Major cause of human reproductive failure • Most human miscarriages are aneuploids

37. Polyploidy • Individuals have three or more of each type of chromosome (3n, 4n) • Common in flowering plants • Lethal for humans • 99% die before birth • Newborns die soon after birth

38. Nondisjunction n + 1 n + 1 n - 1 chromosome alignments at metaphase I n - 1 nondisjunction at anaphase I alignments at metaphase II anaphase II Figure 12.17Page 208

39. Down Syndrome • Trisomy of chromosome 21 • Mental impairment and a variety of additional defects • Can be detected before birth • Risk of Down syndrome increases dramatically in mothers over age 35

40. Turner Syndrome • Inheritance of only one X (XO) • 98% spontaneously aborted • Survivors are short, infertile females • No functional ovaries • Secondary sexual traits reduced • May be treated with hormones, surgery

41. Klinefelter Syndrome • XXY condition • Results mainly from nondisjunction in mother (67%) • Phenotype is tall males • Sterile or nearly so • Feminized traits (sparse facial hair, somewhat enlarged breasts) • Treated with testosterone injections

42. XYY Condition • Taller than average males • Most otherwise phenotypically normal • Some mentally impaired • Once thought to be predisposed to criminal behavior, but studies now discredit

43. Phenotypic Treatments • Symptoms of many genetic disorders can be minimized or suppressed by • Dietary controls • Adjustments to environmental conditions • Surgery or hormonal treatments

44. Genetic Screening • Large-scale screening programs detect affected persons • Newborns in United States routinely tested for PKU • Early detection allows dietary intervention and prevents brain impairment

45. Prenatal Diagnosis • Amniocentesis • Chorionic villus sampling • Fetoscopy • All methods have some risks

46. Preimplantation Diagnosis • Used with in-vitro fertilization • Mitotic divisions produce ball of 8 cells • All cells have same genes • One of the cells is removed and its genes analyzed • If cell has no defects, the embryo is implanted in uterus